1. Field of the Invention
The present invention relates to an immnunoassay and an apparatus for the same. More specifically, the present invention relates to a method and an apparatus for an immunoassay with a magnetic label and a SQUID.
2. Detailed Description of Invention
An immunoassay is a method to detect an antigen or an antibody (mentioned with the word xe2x80x9canalytexe2x80x9d in this specification). For identification or measurement, a label is attached to antibody of an antigen-antibody reaction. Various labels and detection method have been proposed and are frequently used.
In particular, various optical methods are well known. In these methods, labels with light, fluorescence or color are used. However, optical methods have too short a sensitivity time for many applications.
As another method, a method using radioactive label is known. However, this method has problems concerning safety which limit its applicability.
Furthermore, there is methods with magnetic labels as a reemergence measurement or a magnetic relaxation method. However, in this method, grain size of the label influences the measured value seriously. Therefore, accuracy of measurement of this method is not stable.
On the other hand, a SQUID has recently been put to practical use. The SQUID comprises a circular current load and one or two Josephson junction(s) on the load. The SQUID has a very high sensitivity compared with a Hall device or a flux gate and is used as a magnetism sensor.
A new assessment method with magnetic label has been developed in accordance with the invention. In this method, it is expected that labels can be detected by a SQUID with high accuracy. However, there is no known practical method to use a SQUID in this context. Magnetic labels have to be magnetized for detection by a SQUID. However, a strong magnetic field of dozens of gauss is necessary for the label to be magnetized.
On the other hand, a SQUID has a very high sensitivity. Therefore, a serious problem occurs in that a SQUID receives the effects of the magnetic field of magnetization means and the desired measured value of the label changes.
Furthermore, an analyte is actually treated with a prepared slide. But, a strong magnetic field magnetizes the prepared slide. Therefore, it is difficult to detect only a label.
The present invention provides a method for an immunoassay with magnetized label and SQUID, which comprising following processes;
(1) an analyte is labeled with a magnetic material label to detect antigen-antibody reaction,
(2) the magnetic material label is magnetized by a magnetic field,
(3) the magnetized magnetic material label detected by a SQUID which detect a magnetic field having right angle to the magnetic field.
In method of the present invention, labels are magnetized and detected by a SQUID. According to a preferable embodiment of the present invention, the magnetic field for magnetization is a static magnetic field.
According to another preferable embodiment of the present invention, an analyte is inspected while moving parallel to the flux forming the magnetic field inside the detection region of the SQUID. Then, the SQUID detects a variation of magnetic field occurred by the moving labels magnetized in particular direction.
At the same time, the present invention contains an apparatus to execute the method provided by the present invention. The apparatus comprises a magnetic field generation means that generates a magnetic field to magnetize the labels. The apparatus comprises a SQUID that measures the magnetic field.
It is preferable that the apparatus comprises a trsportation means which moves the analyte with the magnetized label parallel to the magnetic field generated by the magnetic field generation means.
Furthermore, the apparatus preferably comprises magnetic field compensation means. The compensation means generates a magnetic field parallel to the detection direction of the SQUID. The magnetic field for compensation cancels the magnetic field is at a right angle to the magnetic field for magnetization. Because, the magnetic field for magnetization contains a component that has a right angle to the desired magnetic field and the SQUID has very high sensitivity to detect the component.
According to the preferable embodiment of the present invention, the SQUID is formed of an oxide superconducting thin film having a high critical temperature. By the way, the sensitivity of a SQUID is proportional to the third power of the distance between the SQUID and the analyte. The oxide superconducting materials can be used with a small cooling-systems. The use of the oxide superconducting materials is advantageous in this point.
It is an important characteristic of the present invention that the magnetic field for magnetization is at a right angle to the magnetic field detected by the SQUID. That is to say, in a prior art, the magnetic field for magnetization and the magnetic field detected are parallel to each other. Therefore, the SQUID also detects the magnetic field for magnetization.
On the contrary, in apparatus of the present invention, the magnetic fields are arranged at right angles to each other. The SQUID detects a flux at a right angle to its circular current load and never detects a flux parallel to the circular current load. Therefore, in an apparatus provided by the present invention, the SQUID does not detect the magnetic field for magnetization. In a method using a SQUID of the prior art, a magnetic field for magnetization is an alternative and a noise is offset by using a lock in amplifier.
According to a preferable embodiment of the present invention, a static magnetic field can be used. Because, the static magnetic field can be easily compensated by simple means with a solenoid.
However, because the SQUID has very high sensitivity, even using the magnetic field for compensation will not compensate the magnetic field for magnetization perfectly. Then, according to a preferable embodiment of the present invention, the SQUID detects a variation of the magnetic field. This variation of magnetic field occurs because of motion of the magnetized label in the detection field. This variation itself is not influenced by the magnetic field of the perimeter.
The above and other objects, features and advantages of the present invention will be apparent from following description of preferred embodiments of the invention with reference to the accompanying drawings.